Transthyretin Amyloid Cardiomyopathy Clinical Trials

• Male or female.

• Age 18 years or above at the time of signing the informed consent.

• Have an established diagnosis of ATTR-CM (wild-type ATTR \[ATTRwt\] or variant ATTR \[ATTRv\]), with cardiac amyloid infiltration, increased left ventricular (LV) wall thickness, and HF.

• Note: Target ATTRv recruitment is approximately 15 percent of the study population.

⁃ Cardiac amyloid infiltration demonstrated by:

∙ Cardiac biopsy positive for TTR amyloid, OR

‣ Grade 2 or 3 cardiac uptake at pyrophosphate (PYP)/diphosphono-1,2-propanodicarboxylic acid (DPD)/ hydroxymethylene diphosphonate (HMDP) scintigraphy with single-photon emission computed tomography (SPECT/CT) combined with an extracardiac biopsy positive for TTR amyloid, OR

‣ Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP scintigraphy with SPECT/CT combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE \& UPIE).

⁃ Notes:

‣ Non-invasive diagnostic pathway will be confirmed by a centralised expert review.

‣ Bone tracer scintigraphy will be conducted using 99m-technetium (Tc)-labelled pyrophosphate (99mTc-PYP), 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), or 99mTc-labeled hydroxymethylene diphosphonate (99mTc-HMDP).

⁃ Increased LV wall thickness, as assessed by centralised review of echocardiography, showing interventricular septal wall thickness greater than or equal to 12 millimeter (mm).

⁃ Chronic HF (New York Heart Association \[NYHA\] Class I-IV) requiring ongoing treatment with a loop diuretic with:

∙ At least 1 documented hospitalisation for HF, OR

‣ History of HF manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath, signs of pulmonary congestion on x-ray or auscultation, or peripheral oedema).

‣ Expected to be on stable cardiovascular medical therapy (defined as no greater than 50 percent dose adjustment and no categorical changes of medications), with the exception of diuretics, 4 weeks prior to the randomisation visit.

‣ Completed more than 50 meters on the 6MWT at screening.